TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14834	44725;44726;44727	chr2:178625321;178625320;178625319	chr2:179490048;179490047;179490046
N2AB	13193	39802;39803;39804	chr2:178625321;178625320;178625319	chr2:179490048;179490047;179490046
N2A	12266	37021;37022;37023	chr2:178625321;178625320;178625319	chr2:179490048;179490047;179490046
N2B	5769	17530;17531;17532	chr2:178625321;178625320;178625319	chr2:179490048;179490047;179490046
Novex-1	5894	17905;17906;17907	chr2:178625321;178625320;178625319	chr2:179490048;179490047;179490046
Novex-2	5961	18106;18107;18108	chr2:178625321;178625320;178625319	chr2:179490048;179490047;179490046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-99
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.1706
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
Q/P	None	None	0.202	N	0.506	0.195	0.1749357433	gnomAD-4.0.0	6.86964E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01635E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
Q/A	0.2051	likely_benign	0.1946	benign	-1.267	Destabilizing	0.006	N	0.449	neutral	None	None	None	None	N
Q/C	0.5086	ambiguous	0.4854	ambiguous	-0.803	Destabilizing	0.781	D	0.549	neutral	None	None	None	None	N
Q/D	0.4966	ambiguous	0.5404	ambiguous	-2.016	Highly Destabilizing	0.064	N	0.413	neutral	None	None	None	None	N
Q/E	0.095	likely_benign	0.0956	benign	-1.742	Destabilizing	0.011	N	0.408	neutral	N	0.424148831	None	None	N
Q/F	0.5417	ambiguous	0.5279	ambiguous	-0.699	Destabilizing	0.076	N	0.597	neutral	None	None	None	None	N
Q/G	0.3366	likely_benign	0.3415	ambiguous	-1.699	Destabilizing	0.033	N	0.503	neutral	None	None	None	None	N
Q/H	0.1948	likely_benign	0.1865	benign	-1.261	Destabilizing	0.47	N	0.469	neutral	N	0.447413739	None	None	N
Q/I	0.2571	likely_benign	0.2429	benign	-0.086	Destabilizing	0.076	N	0.511	neutral	None	None	None	None	N
Q/K	0.1117	likely_benign	0.1186	benign	-0.625	Destabilizing	None	N	0.152	neutral	N	0.344250997	None	None	N
Q/L	0.1164	likely_benign	0.1072	benign	-0.086	Destabilizing	None	N	0.379	neutral	N	0.4474761	None	None	N
Q/M	0.254	likely_benign	0.2375	benign	0.076	Stabilizing	0.367	N	0.489	neutral	None	None	None	None	N
Q/N	0.3333	likely_benign	0.3469	ambiguous	-1.453	Destabilizing	0.064	N	0.415	neutral	None	None	None	None	N
Q/P	0.8172	likely_pathogenic	0.8278	pathogenic	-0.454	Destabilizing	0.202	N	0.506	neutral	N	0.451179941	None	None	N
Q/R	0.1219	likely_benign	0.1229	benign	-0.759	Destabilizing	None	N	0.248	neutral	N	0.413043409	None	None	N
Q/S	0.2098	likely_benign	0.1949	benign	-1.708	Destabilizing	0.001	N	0.191	neutral	None	None	None	None	N
Q/T	0.1326	likely_benign	0.1223	benign	-1.248	Destabilizing	0.001	N	0.289	neutral	None	None	None	None	N
Q/V	0.1869	likely_benign	0.1695	benign	-0.454	Destabilizing	0.033	N	0.498	neutral	None	None	None	None	N
Q/W	0.4685	ambiguous	0.4717	ambiguous	-0.723	Destabilizing	0.931	D	0.528	neutral	None	None	None	None	N
Q/Y	0.3543	ambiguous	0.3524	ambiguous	-0.363	Destabilizing	0.251	N	0.547	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.